Ammonia

Identification

Brand Names

Kenalog

Generic Name

Ammonia

DrugBank Accession Number

DB11118

Background

Ammonia is a naturally-occurring compound with a chemical formula NH3 and structure of trigonal pyramidal geometry. It is a colorless gas with a pungent smell, and become NH4, or ammonium ion, when in water. Although ammonia is used as a food additive in the anhydrous form and serves as a starting material in pharmaceutical and commercial products, it is caustic and hazardous when concentrated. Ammonia gas has been used in the clinical setting as a respiratory stimulant to prevent fainting. The radiolabelled form of ammonia, ammonia N 13, is intravenously administered as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the myocardium to evaluate myocardial perfusion. Ammonia is a natural byproduct of biological and chemical reactions, including decomposition of organic matter, including plants, animals, and animal wastes. It is present in normally present in all tissues constituting a metabolic pool, where it is mostly taken up by glutamic acid and take part in transamination and other reactions, including the synthesis of protein by the Krebs-Hanseleit cycle in the liver ⁵. It is proposed that human adults produce about 1000 mmol of ammonia daily, most of which undergoes excretion in the urine.

Type

Small Molecule

Groups

Approved

Synonyms

Not Available

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Pharmacology

Indication

• Indicated for use as a smelling salt to treat or prevent fainting.
• (when radiolabelled) Indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease ^Label.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Skin irritation		••• •••			•••• ••••••
Prophylaxis of	Faintness/fainting		••• •••			•••••••

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Pharmacodynamics

As a gas, ammonia is a natural byproduct and respiratory stimulant. Its renal metabolism plays a role in whole body acid-base balance.

Mechanism of action

Renal excretion and metabolism of ammonia is critical in regulation of acid-base balance by generating bicarbonate ions and promoting renal net acid excretion, both under basal conditions and in response to acid-base disturbances ⁴. There is evidence that acute ammonia exposure activates NMDA receptor signalling pathways, and high concentrations of ammonia resulting from urea cycle enzyme deficiencies are associated with changes in astrocyte morphology due to glutamine accumulation, changes in the expression of key astrocyte proteins, and increased concentrations of neuroactive L-tryptophan metabolites ².

Absorption

Ammonia can be absorbed via oral or inhalation route. Inhales ammonia is temporarily dissolved in the mucus of the upper respiratory tract, however the majority of the gas is released back into the air via expiration ⁵. In healthy male subjects under exposure to 500 ppm ammonia for 10-27 minutes, about 70-80% of total inspired ammonia was expired ⁵. In extrahepatic tissues such as the intestine, ammonia is incorporated into nontoxic glutamine and released into blood, where it is transported to the liver for ureagenesis ⁵.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Healthy hepatocytes detoxify ammonia where hepatic glutaminase, glutamine synthetase and the urea cycle enzymes act as major enzymes for ammonia metabolism. Ammonia is converted to urea in the liver and other tissues. Glutaminase and glutamine synthetase catalyze the condensation of ammonia with glutamate to glutamine, which is a common nontoxic carrier of ammonia ³. In case of hepatic dysfunction or impairment, detoxification capacity decreases and may cause severe pathologies from hyperammonemia, such as hepatic encephalopathy ⁵.

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• Ammonia
  • Urea

Route of elimination

It is mainly excreted through expired air or renal elimination ⁵.

Half-life

In normal rat brain, blood-derived ammonia was rapidly converted to glutamine, indicating very short half-life of less than 3 seconds ⁵.

Clearance

Not Available

Adverse Effects

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Toxicity

LC50 via inhalation in rat is 7338 ppm/1h ^MSDS. High exposure to ammonia can cause pulmonary edema, which may be life-threatening. Exposure can cause headache, loss of sense of smell, nausea, and vomiting. While mammals has various mechanisms to detoxify and excrete ammonia from the body, death has been reported after an exposure to 10,000 ppm for an unknown duration. Bradycardia was seen at 2,500 ppm, and hypertension and cardiac arrhythmias leading to cardiovascular collapse followed acute exposures to concentrations exceeding 5,000 ppm ⁵.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Not Available

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Ammonia	Inhalant	0.045 g/0.3mL	Respiratory (inhalation)	Physicians Total Care, Inc.	2012-08-17	2013-01-15
Ammonia Inhalants	Inhalant	0.045 g/0.3mL	Respiratory (inhalation)	A-S Medication Solutions	1976-02-14	Not applicable
Ammonia Inhalants	Inhalant	0.045 g/0.3mL	Respiratory (inhalation)	XGen Pharmaceuticals DJB, Inc.	1976-02-14	2020-09-25
Ammonia Inhalants	Inhalant	0.045 g/0.3mL	Respiratory (inhalation)	Remedy Repack	2015-03-24	2017-03-21
Ammonia Inhalants	Inhalant	0.045 g/0.3mL	Respiratory (inhalation)	Sina Health Inc	1976-02-14	Not applicable

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
4010 First Aid Kit	Kit	0.045 g/0.3mL	Topical	Honeywell Safety Products USA, Inc.	2018-10-14	2019-10-18
After Bite Liquid 3.61%	Liquid	3.61 %	Topical	Tender Corporation	1990-12-31	1998-09-11
After Bite Outdoor	Liquid	3.5 g/100g	Topical	Tender Corporation	2014-11-25	2016-11-01
After Bite The Itch Eraser KIDS	Liquid	3.5 g/100g	Topical	Tender Corporation	2014-11-25	2014-11-25
After Bite The Itch Eraser Xtra	Liquid	3.5 g/100g	Topical	Tender Corporation	2014-11-25	2014-11-26

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
4032 First Aid Kit	Ammonia (0.045 g/0.3mL) + Acetylsalicylic acid (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (24.64 mg/1mL) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Inhalant; Kit; Liquid; Ointment; Spray; Tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4076 First Aid Kit	Ammonia (0.045 g/0.3mL) + Acetaminophen (325 mg/1) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Ethanol (0.5 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g) + Neomycin sulfate (3.5 mg/1g) + Water (98.6 mL/100mL)	Kit	Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4121 First Aid Kit	Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzalkonium chloride (0.13 g/100g) + Lidocaine hydrochloride (0.5 g/100g) + Water (98.6 mL/100mL)	Kit	Ophthalmic; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc.	2019-01-24	2019-10-18
4125 First Aid Kit	Ammonia (0.045 g/0.3mL) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzethonium chloride (0.2 g/100g) + Benzocaine (10 g/100g) + Benzocaine (10 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Menthol (0.33 g/100g) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Inhalant; Kit; Liquid; Ointment; Spray; Swab	Ophthalmic; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4129 First Aid Kit	Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzocaine (20 g/100g) + Ethanol (0.5 mL/1mL) + Hydrocortisone acetate (1 g/100g) + Hydrocortisone acetate (1 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Povidone-iodine (10 mg/1mL)	Kit	Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
4010 First Aid Kit	Ammonia (0.045 g/0.3mL)	Kit	Topical	Honeywell Safety Products USA, Inc.	2018-10-14	2019-10-18
4032 First Aid Kit	Ammonia (0.045 g/0.3mL) + Acetylsalicylic acid (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (24.64 mg/1mL) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Inhalant; Kit; Liquid; Ointment; Spray; Tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4076 First Aid Kit	Ammonia (0.045 g/0.3mL) + Acetaminophen (325 mg/1) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Ethanol (0.5 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g) + Neomycin sulfate (3.5 mg/1g) + Water (98.6 mL/100mL)	Kit	Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable
4121 First Aid Kit	Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzalkonium chloride (0.13 g/100g) + Lidocaine hydrochloride (0.5 g/100g) + Water (98.6 mL/100mL)	Kit	Ophthalmic; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc.	2019-01-24	2019-10-18
4125 First Aid Kit	Ammonia (0.045 g/0.3mL) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzethonium chloride (0.2 g/100g) + Benzocaine (10 g/100g) + Benzocaine (10 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Menthol (0.33 g/100g) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL)	Inhalant; Kit; Liquid; Ointment; Spray; Swab	Ophthalmic; Respiratory (inhalation); Topical	Honeywell Safety Products USA, Inc	2018-10-18	Not applicable

Categories

Drug Categories

• Gases
• Nitrogen Compounds
• Respiratory System Agents

Classification

Not classified

Affected organisms

Not Available

Chemical Identifiers

UNII

Not Available

CAS number

7664-41-7

InChI Key

Not Available

InChI

Not Available

IUPAC Name

Not Available

SMILES

Not Available

References

General References

1. KESEL RG, O'DONNELL JF, et al.: The biological production and therapeutic use of ammonia in the oral cavity in relation to dental caries prevention. J Am Dent Assoc. 1946 Jun;33:695-714. [Article]
2. Felipo V, Butterworth RF: Neurobiology of ammonia. Prog Neurobiol. 2002 Jul;67(4):259-79. [Article]
3. Hakvoort TB, He Y, Kulik W, Vermeulen JL, Duijst S, Ruijter JM, Runge JH, Deutz NE, Koehler SE, Lamers WH: Pivotal role of glutamine synthetase in ammonia detoxification. Hepatology. 2017 Jan;65(1):281-293. doi: 10.1002/hep.28852. Epub 2016 Nov 12. [Article]
4. Weiner ID, Verlander JW: Ammonia Transporters and Their Role in Acid-Base Balance. Physiol Rev. 2017 Apr;97(2):465-494. doi: 10.1152/physrev.00011.2016. [Article]
5. Ammonia - National Library of Medicine HSDB Database - Toxnet - NIH [Link]

External Links

PubChem Substance

347911125

RxNav

1299884

Wikipedia

Ammonia

FDA label

Download (264 KB)

MSDS

Download (242 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Recruiting	Diagnostic	N-13 Ammonia Safety	1
2	Completed	Treatment	Phenylketonuria (PKU)	2
2	Recruiting	Diagnostic	Sickle Cell Disease (SCD)	1
2	Terminated	Treatment	Microvascular coronary artery disease	1
1	Completed	Basic Science	Alteration of Cognitive Function / Military Activity / Military Combat Stress Reaction / Sleep / Sleep Deprivation	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Kit	Topical	0.045 g/0.3mL
Inhalant; kit; liquid; ointment; spray; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Gel; inhalant; kit; liquid; ointment	Ophthalmic; Respiratory (inhalation); Topical
Kit	Ophthalmic; Oral; Respiratory (inhalation); Topical
Kit	Respiratory (inhalation); Topical
Kit	Ophthalmic; Respiratory (inhalation); Topical
Inhalant; kit; liquid; spray; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Gel; inhalant; kit; liquid; ointment; swab	Ophthalmic; Respiratory (inhalation); Topical
Cream; inhalant; kit; swab; tablet	Oral; Respiratory (inhalation); Topical
Kit	Oral; Respiratory (inhalation); Topical
Inhalant; kit; liquid; ointment; spray; swab	Ophthalmic; Respiratory (inhalation); Topical
Cream; inhalant; kit; liquid	Ophthalmic; Respiratory (inhalation); Topical
Inhalant; kit; swab	Respiratory (inhalation); Topical
Inhalant; kit; liquid; ointment; spray; swab; tablet	Ophthalmic; Oral; Respiratory (inhalation); Topical
Kit	Irrigation; Ophthalmic; Respiratory (inhalation); Topical
Kit	Irrigation; Oral; Respiratory (inhalation); Topical
Kit	Irrigation; Ophthalmic; Oral; Respiratory (inhalation); Topical
Liquid	Topical	3.61 %
Liquid	Topical	3.5 g/100g
Aerosol	Respiratory (inhalation)	0.15 g/1g
Aerosol	Respiratory (inhalation)	0.045 g/0.3mL
Swab	Respiratory (inhalation)	15 %
Inhalant	Respiratory (inhalation)	0.045 g/0.3mL
Inhalant	Respiratory (inhalation)	0.05 g/0.33mL
Inhalant	Respiratory (inhalation)	0.15 g/1g
Liquid	Respiratory (inhalation)
Inhalant	Respiratory (inhalation)	10 mL/100mL
Liquid	Topical	7 mg/1mL
Kit	Topical
Kit	Topical	30 mg/1mL
Kit	Oral
Liquid	Nasal; Respiratory (inhalation)
Inhalant	Respiratory (inhalation)	0.013 mL/0.3mL
Kit	Infiltration; Intra-articular; Intramuscular; Respiratory (inhalation); Topical
Inhalant; injection, solution; injection, suspension; kit; solution	Epidural; Infiltration; Intra-articular; Intracaudal; Intramuscular; Perineural; Respiratory (inhalation); Topical
Liniment	Topical
Liquid	Topical
Lotion	Topical	1.5 g/100mL
Kit	Epidural; Infiltration; Intra-articular; Intracaudal; Intramuscular; Perineural; Respiratory (inhalation); Topical
Liquid	Topical	20 mg/1mL
Solution	Cutaneous
Syrup
Solution	Nasal	2.5 mg/100mL
Solution	Nasal	2.5 g/100mL
Elixir	Nasal	2.5 g/100mL

Prices

Not Available

Patents

Not Available

Properties

State

Gas

Experimental Properties

Property	Value	Source
melting point (°C)	-77.7	MSDS
boiling point (°C)	-33.4	MSDS

Predicted Properties

Not Available

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

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Drug created at December 03, 2015 16:51 / Updated at June 12, 2020 16:53